Inflammatory cells in the synovial membrane and the synovial fluid of patients with rheumatoid arthritis (RA) are derived from peripheral blood and the migration of these cells to synovial membranes has not been explicated perfectly yet, but it is believed to be caused by a complicated interaction between chemical signals given to cells and protein (adhesion molecule) on cell membranes.
Various studies upon the significance of membrane proteins in arthritis have been performed. For example, it is known that an intercellular adhesion molecule-1 (hereinafter referred to as ICAM-1)is expressed on the inner layer of the synovial membrane and the blood vessel of the synovial membrane of patients with rheumatoid arthritis (RA), which is a ligand of a T cell surface molecule LFA-1 and causes both adhesion and migration of cells in the blood vessel wall Hale et al.; Arthritis Rheum., 32:22 (1989), and Hayes et al.; Springer Semin. Immunopathol., 11:163 (1989)!.
Similarly, it is suggested that a vasocellular adhesion molecule-1 (hereinafter referred to as VCAM-1), which is a ligand of intergrin VLA-4 expressed on T lymphoid cells (memory cells in particular) and monocytes, is expressed on the synovial membrane and fibroblast-like synovial cells of rheumatoid arthritis (RA) and osteoarthritis, Morales-Ducret et al.; J. Immunol., 149:1424 (1992)!, and further that a membrane protein called VAP-1 is expressed on the endothelial vein of a synovial membrane and may work as a specific recognition structure of leukocytes Salm; et al.; Science, 257, 1407 (1992)!.
The present inventors have engaged in extensive studies with a view to investigating the function of the bone marrow microenvironments in disorders causing abnormalities of B cells, and have found that the pre-B cell growth-supporting ability of bone marrow stromal cells derived from patients with rheumatoid arthritis (RA) and multiple myeloma (MM) is enhanced in comparison with that of healthy donor-derived bone marrow stromal cells and that the direct contact of pre-B cells with stromal cells might play an essential role in this supporting ability. And the present inventors have established novel stromal cell lines (RASV5-5, MMSV3-3) containing a molecule enhancing the growth of pre-B cells by cell-lining stromal cells of patients, and have found that the pre-B cell growth-supporting activity of these stromal cell lines is most likely caused by unknown adhesion molecules different from known stem cell factors (SCF), ICAM, CD44, VCAM-1, LFA-1.alpha., LFA-1.beta., NCAM and FLAM-1 J. Immunol., 149:4088 (1992)!.
Further, since it has been suggested that the synovial cell line SynSV6-14 established from the synovial cell derived from patients with rheumatoid arthritis (RA) has pre-B cell growth-supporting ability similarly to the stromal cell line RASV5-5 derived from the bone marrow of patients with rheumatoid arthritis (RA), the present inventors have obtained a novel monoclonal antibody which responds to these cell lines but does not respond to the stromal cell line NFSV1-1 derived from the human bone marrow having no pre-B cell growth-supporting ability, and at the same time have succeeded in cloning genes encoding its antigen membrane protein (Bst-1) (Japanese Patent Application No. 5-141178/1993).